Sharpless epoxidation transform

A catalytic enantio- and diastereoselective dihydroxylation procedure without the assistance of a directing functional group (like the allylic alcohol group in the Sharpless epox-idation) has also been developed by K.B. Sharpless (E.N. Jacobsen, 1988 H.-L. Kwong, 1990 B.M. Kim, 1990 H. Waldmann, 1992). It uses osmium tetroxide as a catalytic oxidant (as little as 20 ppm to date) and two readily available cinchona alkaloid diastereomeis, namely the 4-chlorobenzoate esters or bulky aryl ethers of dihydroquinine and dihydroquinidine (cf. p. 290% as stereosteering reagents (structures of the Os complexes see R.M. Pearlstein, 1990). The transformation lacks the high asymmetric inductions of the Sharpless epoxidation, but it is broadly applicable and insensitive to air and water. Further improvements are to be expected. 

Another interesting application of the deoxygenation reaction is shown in Scheme 12.6. Sharpless epoxides are transformed to enantiomerically pure allylic alcohols [14]. It should be noted that the disadvantage of the loss of one-half of the allylic alcohol, as in the case of kinetic resolutions of allylic alcohols, is not a problem when this protocol is employed. 

It is instructive to compare the properties of metal peroxo and alkyl (or hydro) peroxo groups for the case of Ti because experimental structures of both types are known [117, 119-121] and Ti compounds are catalysts for such important processes as Sharpless epoxidation [22] and epoxidation over Ti-silicalites [122], where alkyl and hydro peroxo intermediates, respectively, are assumed to act as oxygen donors. Actually, the known Ti(t 2-02) complexes are not active in epoxidation. [121-124] However, there is evidence [123] that (TPP)Ti(02) (TPP = tetraphenylporphyrin) becomes active in epoxidation of cyclohexene when transformed to the cis-hydroxo(alkyl peroxo) complex (TPP)Ti(OH)(OOR) although the latter has never been isolated. 

Scheme 13 Intramolecular HWE reaction and Sharpless epoxidation as key transformations toward stolonidiol (38)...

Ikegami has devised an interesting approach based upon 1,3-cyclooctadiene monoepoxide as starting material (Scheme LX) Transannular cyclization, Sharpless epoxidation, and silylation leads to 638 which is opened with reasonable regioselec-tivity upon reaction with l,3-bis(methylthio)allyllithium. Once aldehyde 639 had been accessed, -amyllithium addition was found to be stereoselective, perhaps because of the location of the te -butyldimethylsilyloxy group. Nevertheless, 640 is ultimately produced in low overall yield. This situation is rectified in part by the initial formation of 641 and eventual decarboxylative elimination of 642 to arrive at 643. An additional improvement has appeared in the form of a 1,2-carbonyl transposition sequence which successfully transforms 641 into 644... 

Sharpless epoxidation of (E)-(l,2-dialkyl)vinylsilanols 13, prepared from hydrolysis of ( )-( 1,2-dialkyl )vinyldimethylbutoxysilanes 12, gave silylepoxides 14, which were treated with Et4NF in MeCN to afford epoxides 15 in 62-70% overall yield and 44-70% ee (Scheme 6AA.6).7 The overall transformation can be considered as asymmetric epoxidation of simple internal alkenes. This approach was applied to the synthesis of a naturally occurring insect sex pheromone (+)-disparlure.7... 

Compared to the Sharpless Epoxidation, the Jacobsen Epoxidation allows a broader substrate scope for the transformation good substrates are conjugated c/s-olefins or alkyl-substituted cis-olefins bearing one bulky alkyl group. 

There are two reasons for this. First, the Sharpless epoxidation can be applied to almost all primary and secondary allylic alcohols. Second, it makes trifimctional compounds accessible in the form of enantiomerically pure ,/1-epoxy alcohols. These can react with a wide variety of nucleophiles to produce enantiomerically pure second-generation products. Further transformations can lead to other enantiomerically pure species that ultimately may bear little structural resemblance to the starting a,/1-epoxy alcohols. 

Our synthesis of corossolin started from the cheap sugar material, D-glucono-5-lactone, whose C-3 and C-4 stereogenic centers were introduced into the target as C-19 and C-20, respectively. Subsequent introduction of C-15 and C-16 was achieved by Sharpless epoxidation of an allylic alcohol intermediate, and then the THF core 14 was established through a couple steps of transformations. On... 

The combination of Ti(OPr )4 and (BulO)2 or Bu 02I I has been utilized in a number of organic transformations including the Sharpless epoxidation,416 the conversion of alcohols to carbonyl compounds,417 the oxidation of phenols to quinones or ketols,418 and the oxidation of Ti enolates to o-hydroxyketones.419... 

Asymmetric oxidations have followed the usual development pathway in which face selectivity was observed through the use of chiral auxiliaries and templates. The breakthrough came with the Sharpless asymmetric epoxidation method, which, although stoichiometric, allowed for a wide range of substrates and the stereochemistry of the product to be controlled in a predictable manner [1]. The need for a catalytic reaction was very apparent, but this was developed and now the Sharpless epoxidation is a viable process al scale, although subject to the usual economic problems of a cost-effective route to the substrate (see later) [2]. The Sharpless epoxidation has now been joined by other methods and a wide range of products are now available. The pow er of these oxidations is augmented by the synthetic utility of the resultant epoxides or diols that can be used for further transformations, especially those that use a substitution reaction (see Chapter 7) [1]. 

The synthesis of 132, starting from S-benzyloxy propanal (131), involved the ring opening of an optically active epoxide 133 with a xanthate anion (Scheme 37)J22 Stereoselective synthesis of 133 by Sharpless epoxidation allowed preparation of the 2-deoxy-4-thio-D- and L-ezyr/zro-pentoses, " which were transformed into the corresponding pyrimidine nucleosides with silylated uracil and McaSiOTf. and then deprotected with Bu NF. 

The same group has applied this imino Diels-Alder reaction in an enantiosel-ective total synthesis of the alkaloid (-)-cannabisativine (Scheme 33) [70b]. An initial Sharpless epoxidation of allylic alcohol 183 provided enantiomerically pure compound 184, which could be converted in four steps to alcohol 185. This compound could then be relayed into the requisite diene 186. Imino Diels-Alder reaction of 186 led to a single cycloadduct 188, presumably via a transition state like 187. It was then possible to homologate the ester functionality of 188 via the corresponding aldehyde to acetal 189. This intermediate could be converted in several steps into 190. Another key step in the strategy was epimeriza-tion via a retro Michael reaction leading to aldehyde 191, which could be transformed in five steps into (-)-cannabisativine. 

The homochiral acetylenic alcohol 2 [derived from ( )-4-benzyloxy-2-butenol by asymmetric Sharpless epoxidation via 2 in four steps] is transformed either to ( )-3 by treatment w ith lithium aluminum hydride or to (Z)-4 by hydrogenation with Lindlar catalyst. Simple Claisen or ortho ester rearrangement yield the same, but enantiomeric, products 5 and 6 with 85-90% ee288. 

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